Is SRM p.Ala15Val (c.44C>T) pathogenic?

SRM p.Ala15Val (c.44C>T) is classified Uncertain significance in SRM (ClinVar, Single submitter, 1 submitter; last evaluated 2023-10-30). AlphaMissense: likely benign (0.1779); Ultra-rare (popmax 0.0193%, sas).

How common is SRM p.Ala15Val (c.44C>T) in the general population?

SRM p.Ala15Val (c.44C>T) is ultra-rare (popmax 0.0193%, sas) (gnomAD).

What do computational predictors say about SRM p.Ala15Val (c.44C>T)?

AlphaMissense predicts likely benign (score 0.1779) — an in-silico prediction, not a clinical call.

SRM p.Ala15Val

c.44C>T · rs750929877 · VCV3170001

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely benign

0.1779 · ACMG-weighted

gnomAD v4.1

Rare

ultra-rare (popmax 0.0193%, sas)

Missense predictors

0/3 damaging

AlphaMissense, REVEL, SaProt

Computational evidence

Protein change
AlphaMissense	0.1779	likely benign
REVEL	0.148	moderately benign-leaning
SaProt	LLR -8.61	tolerated
⇒ AlphaMissense, REVEL and SaProt all call this tolerated.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 8.5	GERP 1.3, phastCons 1
Regional constraint	o/e 0.60	unconstrained · MANE · 5,075 bp · p 3.2e-16 · regional, not allelic
Overall
CADD	21.6	PHRED · no single calibrated threshold — expert panels disagree

ClinVar classifies this uncertain; the computational predictors unanimously lean tolerated — a triage signal, not a reclassification

AlphaMissense carries the ACMG weight for missense; REVEL and SaProt are independent agreement signals.

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.0193% South Asian · 14/72,632 alleles

Filtering AF 0.0116% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.00931%

Overall 0.00112% 16/1,432,016 alleles · ultra-rare exomes 15/1,281,494 · genomes 1/150,522 · joint denominator

Ancestry group	Frequency	1 in
South Asiangrpmax	0.0193%	5,188
Remaining individualsnot grpmax-eligible	0.00185%	54,118
European (non-Finnish)	9.15e-05%	1,093,184

Rarity supports pathogenicity (ACMG PM2); frequency above a disease-specific BA1/BS1 threshold argues against it. A variant frequent in one ancestry group can be near-absent in others, so a single global figure can mislead.

Variant & gene context

Gene: SRM
Protein: p.Ala15Val
Coding: c.44C>T
MANE Select: NM_003132
dbSNP: rs750929877
Type: single nucleotide variant
Location: chr1:11059900 (GRCh38)
Gene constraint: LOEUF 0.593 · pLI 0.64 (gnomAD)
Structure: AlphaFold pLDDT 94.64 · 6 PDB

Full SRM gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Similar variants

SRM p.Ala272Thr Uncertain significance ★ ⚠ same type
SRM p.Ala287Thr Uncertain significance ★ same type
SRM p.Ala84Ser Uncertain significance ★ ⚠ same type
SRM p.Ala9Pro Uncertain significance ★ ⚠ same type
SRM p.Arg17Cys Uncertain significance ★ ⚠ same type
SRM p.Arg285Cys Uncertain significance ★ ⚠ same type
SRM p.Arg285His Uncertain significance ★ ⚠ same type
SRM p.Arg295His Uncertain significance ★ ⚠ same type

Built on 18 open, versioned datasets — ClinVar, gnomAD, AlphaMissense, REVEL, ClinGen & more — plus Sugi Variant's own cross-source analysis. Source data 2026-01–2026-10, ClinVar 2026-10. Full sources & versions →

Cite Sugi Variant

Gür T. Sugi Variant: A Deterministic Per-Variant Germline Reference from a Knowledge Graph for Humans and AI Agents. 2026. doi:10.5281/zenodo.21509445. This variant: https://sugi.bio/variant/srm-p-ala15val (accessed [today's date]).

Preprint & method: sugi.bio/variant/method Machine-readable: this page as Markdown